Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial (NCT02169089), a randomized phase 4 study. The primary outcome is Percent Change in Atheroma Volume (PAV) in the Thoracic Aorta of Spironolactone vs. Placebo.

2. Clinical Question

3. Trial Design

This was a phase 4, randomized, parallel-group trial comparing spironolactone with placebo. The registry identifies the masking as quadruple. It records enrollment of 79 and a completed study. The listed start was 2016-01, and primary completion was 2022-04-29. University Hospitals Cleveland Medical Center is the sponsor. These design features describe how the study was organized; by themselves, they do not establish how participants were selected, how the random sequence was generated, or whether allocation could be concealed.

The registry reports 37 participants in the spironolactone group and 42 in the placebo group for the primary outcome. The primary endpoint was percent change in thoracic aortic atheroma volume over 56 weeks. The brief summary says that MRI pictures of the aortic wall before and after therapy were compared. The record also lists four secondary outcomes: left ventricular mass index, myocardial fibrosis measured as change in native T1, change in 24-hour ambulatory systolic blood pressure, and measures of insulin resistance using HOMA-IR. The blood-pressure outcome has an 11-week timeframe; the other listed secondary outcomes have a 56-week timeframe.

Other details needed to reconstruct the protocol are not reported in the registry record. These include the original sample-size justification, eligibility criteria, treatment dose and schedule, visit schedule, randomization procedures, masking procedures, and the planned analysis populations. The record does not identify a statistical analysis plan or say whether interim analyses were planned. The fact that a study is marked completed does not supply those missing methodological details.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percent Change in Atheroma Volume (PAV) in the Thoracic Aorta of Spironolactone vs. Placebo, measured over 56 weeks.

The primary endpoint is percent change in atheroma volume in the thoracic aorta, compared between spironolactone and placebo at 56 weeks. Atheroma volume refers to the amount of plaque within the artery. The registry describes atherosclerosis as involving fatty deposits and inflammation in artery walls and says that MRI images of the aortic wall were used to compare measurements before and after therapy.

As a general statistical and clinical concept, an imaging measure can be used to quantify changes in the structure of a vessel without waiting for clinical events to occur. Such a measure is distinct from outcomes such as heart attack, stroke, or death: a change in an image-based measure does not by itself establish a corresponding change in those events. The registry frames the study around whether spironolactone might slow worsening of aortic atherosclerotic disease, but it does not report a validated relationship between this endpoint and later clinical outcomes.

The primary outcome is listed as a continuous measure summarized by its mean and standard deviation. The posted arm values describe average percent change, while the comparison describes the difference between group means. The endpoint is therefore interpreted as a group-level change in imaging measurements, not as the proportion of participants who improved or as an individual prediction.

7. Results Posted in the Registry

• Spironolactone: mean 0.50 versus 7.30 on control; difference -6.80 (95% CI -11.59 to -2.01), standardized effect d = -0.62; z-test p = 0.005.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Left Ventricular Mass Index of Spironolactone vs. Placebo.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Spironolactone: mean -3.50 versus 2.10 on control; difference -5.60 (95% CI -7.41 to -3.79), standardized effect d = -1.35; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Spironolactone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Myocardial Fibrosis (Change in Native T1) Spironolactone vs. Placebo

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Spironolactone: mean -10.30 versus 17.10 on control; difference -27.40 (95% CI -43.20 to -11.60), standardized effect d = -0.77; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Spironolactone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in 24-hour Ambulatory Systolic Blood Pressure of Spironolactone vs. Placebo

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Spironolactone: mean -5.95 versus 2.00 on control; difference -7.95 (95% CI -14.32 to -1.58), standardized effect d = -0.54; z-test p = 0.015.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Spironolactone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Across the secondary outcomes, the posted arm summaries and analyses describe differences in several domains: cardiac structure, myocardial tissue characterization, ambulatory systolic blood pressure, and insulin resistance. The reported sponsor analyses identify statistically notable group comparisons for some outcomes, while the blood-pressure sponsor analysis has a p-value of 0.128. Viewed together, the outcomes suggest a pattern that is not uniform across every measure or analysis. They should be read as a set of related observations rather than as separate, definitive answers to the primary question.

The secondary measures can provide context for the primary MRI endpoint because they address other aspects of cardiovascular structure, tissue characteristics, blood pressure, or metabolism. They do not directly establish that a difference in aortic atheroma volume translates into a difference in heart attacks, strokes, death, or other clinical events. Nor does a favorable statistical result on one secondary measure verify the primary result by itself. The record does not report a prespecified hierarchy or an overall combined endpoint connecting these measures.

Unadjusted secondary results carry less weight because multiple outcomes create multiple opportunities for apparently notable findings. General explanation: when many hypotheses are tested separately without a multiplicity procedure, the risk of false-positive findings across the set can be greater than the error rate attached to a single test. The registry record does not report a correction for multiple testing or specify which secondary outcomes were confirmatory. Thus, the secondary results are useful for describing the range of findings, but they should be interpreted cautiously and not treated as independent proof of a common effect.

The endpoint timeframes are not identical: the blood-pressure measure is listed at 11 weeks, whereas the other secondary outcomes are listed at 56 weeks. This makes it important to interpret each measure in its stated timeframe rather than assuming that all outcomes reflect the same point in follow-up. Detailed reasons for the differing timeframes, the order in which outcomes were assessed, and any missing-data procedures are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Left Ventricular Mass Index of Spironolactone vs. Placebo.
• Myocardial Fibrosis (Change in Native T1) Spironolactone vs. Placebo
• Change in 24-hour Ambulatory Systolic Blood Pressure of Spironolactone vs. Placebo
• Measures of Insulin Resistance (HOMA-IR) of Spironolactone vs. Placebo

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a percentage change, and the registry summarizes each group using a mean and standard deviation. The mean describes the arithmetic average of the recorded values. The standard deviation describes how spread out the individual values are around that group average. A standard deviation is not the uncertainty in the mean itself; uncertainty in a group comparison also depends on the number of participants and the analysis method.

What does the mean difference represent?

The recalculated contrast is spironolactone minus placebo. It compares the posted group means and reports the result in the original outcome units, percentage change. A negative mean difference means the spironolactone group had a lower average value than the placebo group. The contrast is unadjusted: it is based on the posted summary statistics and does not account for covariates or other factors. The registry lists a mean difference of -6.8 for the primary outcome.

A difference in means is useful when the outcome is measured on a numeric scale and a comparison of group averages is meaningful. It does not show the full distribution of participant outcomes. Two groups can have different averages while still having substantial overlap among individual values. The arm-level standard deviations provide some information about spread, but the registry summary does not provide participant-level data or distributions.

What does the confidence interval add?

General explanation: a confidence interval describes the uncertainty around an estimated quantity under a particular statistical procedure and its assumptions. It is not a range containing a fixed proportion of individual participant values, nor is it a guarantee that the true value lies within its endpoints. For the recalculated primary mean difference, the 95% confidence interval is -11.59 to -2.014. Its width reflects uncertainty in the estimate; a more precise estimate would generally have a narrower interval, all else being equal. The registry's sponsor analysis does not report a confidence interval for its median-difference estimate.

The recalculated p-value is 0.005. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry also reports a separate sponsor p-value using a Wilcoxon (Mann-Whitney) method. Because the method and summary measure differ, those two p-values answer related but not identical statistical questions.

Why do the analyses use different summaries?

The sponsor's reported analysis uses a Wilcoxon (Mann-Whitney) method and describes its parameter as a median difference in final values. This is a rank-based method; in general, it compares the ordering of observations between groups rather than directly testing a difference between arithmetic means. The posted result is labeled a median difference, but the registry does not provide the detailed computational definition, the confidence interval, or further model specifications. The recalculated analysis instead uses group means and standard deviations to estimate an unadjusted mean difference. Neither result should be relabeled as the other.

For the primary outcome, the recalculated mean comparison uses the posted arm means, standard deviations, and sample sizes. It is not an adjusted analysis and does not reconstruct participant-level data. The registry record does not report whether the sponsor's primary analysis was prespecified in a protocol or statistical analysis plan, whether the reported median-difference procedure was stratified or adjusted, or how missing observations were treated. Those omissions limit how closely an outside reader can reproduce the sponsor's analysis.

What do the secondary comparisons contribute?

The secondary endpoints are also reported as continuous outcomes, with means and standard deviations in the arm summaries. Their recalculated contrasts are unadjusted mean differences. The sponsor reports Wilcoxon (Mann-Whitney) analyses described as median differences in final values. As with the primary endpoint, these are different summaries and analytic approaches. The secondary results can describe whether outcomes moved in different directions across groups, but they should not be treated as independent confirmations without considering the number of outcomes and the analysis plan.

General explanation: when several outcomes are tested, the chance of obtaining at least one apparently notable result by chance can increase if each test is considered separately. Methods that account for multiple testing can address this issue, but the registry record does not report whether any adjustment was planned or used. The posted secondary p-values are therefore best understood as unadjusted reported tests, not as evidence that a multiplicity-controlled family of hypotheses was met.

The record lists five outcome measures and four posted secondary outcomes. It does not identify a hierarchy among the secondary endpoints, describe whether they were exploratory or confirmatory, or report a prespecified procedure for handling multiple comparisons. A reader should consequently give the primary outcome the clearest role in interpreting the trial and regard secondary comparisons as additional, less definitive evidence.

Statistical methods beyond those explicitly described are not reported in the registry record. In particular, the record does not state the original sample-size assumptions, the planned model, any covariate adjustments, the treatment of outliers, or whether assumptions about the distributions were checked. General statistical explanations above clarify the meaning of common summaries, but they should not be mistaken for methods confirmed to have been used in the trial.

11. Confidence Intervals and Precision

The recalculated primary mean difference is -6.8, with a 95% confidence interval from -11.59 to -2.014. The endpoints are both below zero, so the interval does not include zero under this recalculation. Its width indicates that the estimate is not exact: values across a range remain compatible with the data and the calculation's assumptions. The result is more informative than the point estimate alone because it displays uncertainty about the group contrast.

General explanation: a confidence interval is a measure of uncertainty for an estimate, not a description of the range of outcomes among participants. A narrower interval usually indicates greater precision, while a wider interval indicates less precision, when the outcome and method are comparable. The interval does not account for every possible source of uncertainty, including unreported analysis choices, missing data, or limitations in how the endpoint represents clinical outcomes.

The sponsor's primary analysis reports a median-difference estimate of -7.78 but no confidence interval. That omission means its precision cannot be judged from an interval in the registry record. The sponsor-reported p-value, 0.029, provides a test result but does not replace an interval or show the range of estimates compatible with the data.

The recalculated confidence intervals for the secondary mean differences are also reported with the endpoint results, while the sponsor's secondary median-difference analyses do not include confidence intervals. These should not be collapsed into a single measure of precision because they refer to different estimands and methods. More generally, precision is limited by the amount of information available, and the primary outcome summaries include 37 participants in the spironolactone arm and 42 in the placebo arm. The registry record does not report interval estimates for the sponsor analyses or enough detail to assess all sources of uncertainty.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are planning illustrations calculated from the observed effect, rather than the trial's original design justification. The assumptions listed for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set in turn to 100%, 75%, or 50% of the observed effect. The trial's own original sample-size assumptions are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm for a hypothetical study to have an 80% chance of detecting the stated effect under those assumptions, if the assumptions and effect size were correct. The 90% power column gives the corresponding per-arm number for a hypothetical study designed for a 90% chance. These are planning targets, not descriptions of what happened in the completed trial. They do not show the probability that the observed result is true or the probability that the trial's result will replicate.

The planning scenarios use fractions of the observed effect. A smaller effect is harder to distinguish from random variation, so more participants are needed to achieve the same target power under the same assumptions. Consequently, the scenarios based on smaller fractions require larger per-arm sample sizes than those based on the full observed effect. This feature also illustrates how sensitive planning can be to the effect size chosen: an estimate from a relatively small study may not be a stable guide to the effect a future study should expect.

These figures are not observed power. They are prospective planning illustrations based on an effect estimated from the posted results, not a reconstruction of the trial's actual design process. They also do not account for any design features or analysis choices beyond the stated assumptions. The registry record does not report whether the original trial was planned using these assumptions or whether its enrollment target was based on another calculation.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -6.800; pooled standard deviation σ = 10.900.
2. n = 2 × (1.96 + 0.842)² × 10.900² / -6.800² = 40.3, rounded up to 41 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -6.8                      # observed difference in means
sigma <- 10.899541274751                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2169089)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 41 (80% power), 54 (90% power)
 75% of observed effect: n per arm = 72 (80% power), 96 (90% power)
 50% of observed effect: n per arm = 162 (80% power), 216 (90% power)
power.t.test: 41.3 
Simulated power at n = 41 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor's reported primary analysis is a Wilcoxon (Mann-Whitney) comparison described as a median difference in final values. It reports an estimate of -7.78 and p = 0.029. The registry does not report a confidence interval for that estimate. This is the sponsor-reported inferential result and should be kept distinct from the recalculated summary-statistic comparison.

The recalculation uses the posted group means and standard deviations to estimate an unadjusted mean difference in percent change. It gives -6.8, with a 95% confidence interval from -11.59 to -2.014 and p = 0.005. A mean difference in change and a median difference in final values are not the same quantity. Differences in the analysis method and summary measure can produce different estimates and p-values without implying that one is a direct correction of the other.

The registry does not report enough detail to reproduce the sponsor's rank-based analysis, including its full specification and handling of missing observations. The recalculation is therefore supplementary context based on the posted summaries; it does not replace the sponsor's analysis. The record does not flag a discrepancy between the posted and recalculated findings, but both results should still be described according to their own methods and estimands.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and four secondary outcomes, and it reports statistical analyses for the primary endpoint and the four secondary endpoints. It does not report a multiplicity adjustment, a hierarchy for testing the outcomes, or a definition of which secondary results were intended to be confirmatory. Without those details, the reported secondary p-values should be read as individual, unadjusted results rather than as conclusions from a family of tests with controlled error.

General explanation: testing several outcomes increases the opportunity for a low p-value to occur by chance somewhere in the set. Multiplicity procedures can change the threshold for interpreting individual tests or otherwise account for the collection of tests. Whether such a procedure was planned or used in this trial is not reported in the registry record. The primary analysis remains the clearest registered statistical question, while the secondary findings are more exploratory in interpretation unless other protocol details establish otherwise.

Missing-data methods and analysis populations are also not reported in the registry record. The arm summaries show 37 participants for spironolactone and 42 for placebo, but the record does not say whether these are all randomized participants, all participants with an observed endpoint, or a different analysis set. It does not describe how missing MRI measurements or missing secondary outcomes were handled, whether imputation was used, or whether sensitivity analyses assessed the effect of missing data.

The record does not specify whether the analysis followed an intention-to-treat principle, a per-protocol approach, or another population definition. It also does not describe protocol deviations, exclusions after randomization, or the handling of participants who discontinued treatment. These omissions make it difficult to assess whether the posted summaries preserve the benefits of randomization in the analysis and how robust the results are to missing observations.

Interim analyses, stopping rules, and the original statistical analysis plan are not reported in the registry record. The record also does not identify planned covariate adjustment or the full model specification. These details matter when assessing whether reported analyses were chosen in advance and whether the inference accounts for all planned comparisons. Their absence does not prove that such procedures were not used; it means their use cannot be established from the registry record.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: surgical (9.5%), diabetes related (5.4%), infection (5.4%), hyperkalemia (2.7%), chest pain/discomfort (2.7%).

The registry reports serious adverse events in 7 of 37 participants in the spironolactone group and 8 of 42 participants in the placebo group. It reports other adverse events in 9 of 37 and 8 of 42 participants, respectively. Deaths are reported for 1 participant in each group. These counts describe the posted safety summaries; they do not by themselves establish that an event was caused by study treatment or show how event timing related to treatment.

The record lists serious-event terms and percentages, including surgical events at 9.5%, diabetes related events at 5.4%, infection at 5.4%, hyperkalemia at 2.7%, chest pain/discomfort at 2.7%, and injury at 2.4%. The registry does not provide an arm-specific breakdown for these listed terms in the information, nor does it explain the event coding or adjudication process. The event-term percentages should therefore be read as registry-reported descriptions, not as a direct comparison between treatment groups.

Safety counts from a study of this size can describe what was recorded but may not precisely characterize uncommon events. The registry record does not report exposure-adjusted event rates, confidence intervals for adverse-event comparisons, or a detailed account of severity and relatedness beyond the serious-event classification. These summaries are not a basis for individual treatment decisions.

17. What the Result Does, and Does Not, Mean

The posted primary data show a lower mean percentage change in thoracic aortic atheroma volume in the spironolactone group than in the placebo group. The recalculated unadjusted mean difference is -6.8, with a 95% confidence interval from -11.59 to -2.014. The sponsor's separate rank-based analysis reports a median difference in final values of -7.78 and p = 0.029. These results describe group-level comparisons in the registry; they do not establish what happened to every participant.

The endpoint is an MRI-based measure of aortic plaque volume, not a clinical event. A difference in this imaging outcome does not alone show a difference in heart attacks, strokes, death, symptoms, or long-term health. The registry record does not report those outcomes as the primary question, and the posted results cannot establish that the observed imaging comparison predicts a clinical benefit or harm.

The results also do not establish that the same pattern would occur in other populations, under other treatment schedules, or over a longer period. The trial enrolled 79 participants, and important details about eligibility, missing observations, analysis populations, and the original statistical plan are not reported in the registry record. The estimates should be understood within those reporting and study-size limits.

Statistical evidence and clinical importance are separate considerations. A p-value describes compatibility with a statistical null hypothesis under a test's assumptions; it does not measure the magnitude or practical importance of an effect. The confidence interval gives uncertainty around the recalculated mean difference, but it does not resolve questions about clinical relevance, endpoint validity, or the possibility of bias from unreported design and analysis details.

The secondary outcomes add information about other measured domains, but they involve multiple comparisons and do not replace the primary endpoint. The registry record does not report a multiplicity adjustment or a confirmatory hierarchy for those outcomes. Taken together, the posted results are evidence about the measured trial outcomes, not a complete account of treatment effects or a recommendation for care.

18. Why This Trial Matters Statistically

This trial is statistically instructive because the primary outcome is continuous and imaging-based, while the registry reports both group means and a sponsor analysis based on ranks and median differences. These summaries answer related but distinct questions. Showing them separately helps readers avoid treating every reported estimate as if it measured exactly the same contrast. It also illustrates why the analysis method and estimand matter when interpreting a p-value or comparing results.

The recalculated mean difference is accompanied by a confidence interval, which communicates uncertainty in a way that a point estimate or p-value alone cannot. The sponsor-reported analysis has no confidence interval in the registry record, so its precision is less fully described. This contrast highlights the value of reporting effect estimates with uncertainty intervals and clear definitions of the outcome and analysis population.

The trial also has several secondary endpoints across different domains. Such breadth can be informative, but it raises the importance of a prespecified testing strategy and transparent multiplicity reporting. The registry record does not report those details. The results therefore demonstrate why statistical significance across a set of outcomes should not be interpreted without knowing how the outcomes were prioritized and how repeated testing was addressed.

Finally, the sample-size illustrations are based on fractions of an observed effect, rather than the original trial design assumptions. They help explain how assumptions about the effect size influence planning, but they are not evidence of the study's achieved power or proof that its original enrollment was adequate. Separating observed results from planning scenarios is central to sound interpretation of a small clinical trial.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The posted results are based on a study with enrollment of 79, and the primary outcome summaries include 37 participants in the spironolactone group and 42 in the placebo group. Estimates from a study of this size may be uncertain, particularly for outcomes with substantial variability. The recalculated confidence interval displays uncertainty for the primary mean comparison, but the registry does not report a confidence interval for the sponsor's primary analysis.

The primary endpoint is an imaging measure, not a clinical outcome. The registry record does not establish how changes in this measure relate to later cardiovascular events. It also does not report participant-level data, the exact imaging measurement procedures, or information needed to assess measurement reliability. The brief summary describes comparison of MRI images before and after therapy, but further operational details are not reported.

The sponsor analysis and the recalculation differ in method and summary measure: one is described as a median difference in final values using a Wilcoxon (Mann-Whitney) method, while the recalculation estimates a mean difference from posted group summaries. The registry does not give enough detail to reconstruct the sponsor analysis fully or to determine how the analysis handled missing measurements. This complicates direct comparison of the two estimates.

Multiplicity handling, analysis populations, missing-data procedures, and interim analyses are not reported in the registry record. The original sample-size justification and full statistical analysis plan are also not reported. The absence of those details limits assessment of prespecification, selective reporting, robustness to missing data, and the role of the secondary results.

The registry reports serious adverse-event counts and selected event terms, but detailed arm-specific term counts and comparative uncertainty are not given. The available safety summary does not establish causation or precisely characterize uncommon events. These limitations are specific to interpreting the information recorded for this trial and should be considered alongside the endpoint and statistical reporting limitations.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial — NCT02169089.
• Registry record last updated 2023-08-01; status last verified 2023-07.
• Results first posted 2023-08-01.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT02169089 is a completed phase 4 randomized, quadruple-masked, parallel-group trial sponsored by University Hospitals Cleveland Medical Center. It enrolled 79 participants and compared spironolactone with placebo in people described in the brief summary as having diabetes and atherosclerotic disease. The primary outcome was percent change in thoracic aortic atheroma volume at 56 weeks.

The posted arm means were 0.5 for spironolactone and 7.3 for placebo. The recalculated unadjusted mean difference was -6.8, with a 95% confidence interval from -11.59 to -2.014 and p = 0.005. The sponsor-reported Wilcoxon (Mann-Whitney) analysis described a median difference in final values of -7.78 and p = 0.029. The methods and estimands differ, so these results should be read separately.

The record also includes four secondary outcomes and adverse-event summaries. Details on the original sample-size justification, multiplicity, missing data, analysis populations, and full statistical plan are not reported in the registry record.